The James Buchanan Brady Urological Institute
 
 
 
                   A PUBLICATION OF THE PATRICK C . WALSH PROSTATE CANCER RESEARCH FUND

   Collision Science, Creative Thinking, and Hope for Treating
   Metastatic Cancer
    

      Meet Our New Research Director: Ken Pienta             

       Volume 10, Winter 2014

Kenneth Pienta
Out-of-the-box scientific thinkers: Ken Pienta, by the portrait of his mentor,
Don Coffey.
Ken Pienta has come home, and it's not to rest on his many laurels, but to challenge himself and the other scientists here at the Brady to find creative new ways to tackle the toughest areas of disease.

In January 2013, Pienta, M.D., succeeded Robert Getzenberg as Director of Research at the Brady – a role held for more than three decades by the legendary Don Coffey, Ph.D. In taking Coffey's old job, Pienta has big shoes to fill, and he knows it well; after earning his M.D. at the Johns Hopkins School of Medicine in 1986, Pienta did his fellowship in medical oncology at the Brady from 1988 to 1991, and Coffey was his mentor. Now, Pienta is the Donald S. Coffey Professor of Urology and Professor of Oncology and Pharmacology and Molecular Sciences at the Johns Hopkins University School of Medicine. Like Coffey, the Catherine Iola and J. Smith Michael Distinguished Professor of Urology, Pienta was very interested in how the structure and function of cells changed in cancer. After his fellowship, Pienta joined the faculty at the University of Michigan, where he established himself as one of the country's leading researchers of prostate cancer, and was repeatedly named one of America's top doctors for treating it. At Michigan, Pienta was the Director of Precision Medicine for the Michigan Center for Translational Pathology; he also served as Vice President for Research, Health Sciences, and was the Director of the Prostate Specialized Program of Research Excellence (SPORE) in addition to teaching, doing research, and seeing patients. In the midst of all of these responsibilities, Pienta made it a point to maintain an active clinical practice taking care of men with advanced prostate cancer. Why do this? One reason is that scientists tend to get so focused on solving their particular piece of the puzzle that they lose sight of the bigger picture of having cancer – the worry, the fatigue, side effects from medications, what it's like for patients and their families to deal with a major illness. "Keeping the patients front and center is a constant reminder of why we're doing this," he says, "why it's so important that we find better ways to treat cancer."


Collision Science

Pienta's website (kenpienta.com) features this quote from Mahatma Gandhi: "You must be the change you wish to see in the world." He is the author of more than 350 journal articles and has been the lead investigator of many clinical trials; he has twice received the American Cancer Society's Clinical Research Professor Award. But throughout his career, Pienta has tried to avoid ever becoming the stereotypical ivory tower academic type, jealously hoarding his research until the next peer-reviewed publication comes out. Early on, Don Coffey taught him to be generous with what he learned. "He always said to make sure to disseminate what you know, and not to worry about being scooped," says Pienta. "I have always tried to stay true to Don's philosophy. At Michigan, when we collected prostate tissue through our tissue acquisition program we gave samples freely throughout the world whenever researchers asked. Over the years, that eventually led to many scientific discoveries." This way of thinking also led Pienta toward what he calls "collision science" – basically, "taking folks from disparate disciplines and getting them to work together at solving problems in the field we are interested in." Although Pienta's own specialty is in treating and studying prostate cancer, "one of my closest research collaborators is a dentist." Why? Dentists are bone biologists, Pienta explains, and that's where advanced prostate cancer tends to spread – the bone.

 

Pienta has also studied "cooperation theory," as it applies to cancer research, with a professor in the School of Public Policy at Michigan. This collaboration has led to a half-dozen projects Pienta has ongoing with biomedical engineers. "We are trying to create little gadgets that will help us get cells out of the blood." As Director of Research at the Brady, Pienta is fostering an environment where this kind of out-of-the-box thinking and multidisciplinary collaboration can thrive. It has to, he says. "So many of the researchers who trained at the Brady over the years are now directing or working at top-notch programs at other institutions. This creates strong competition, which is good. If we want to remain number one, we have to be the best by continuing to make new and important discoveries and working even harder." Pienta, who was named Distinguished Mentor of the Year in 2009 by the American Urological Association, believes that his role is to understand "what everyone's goals are and then figuring out how best to help each one achieve them."


Scientists tend to get so focused
on solving their particular piece of
the puzzle that they lose sight of
the bigger picture of having cancer
– the worry, the fatigue, side effects
from medications, what it's like
for patients and their families to
deal with a major illness.


Cancer Ecosystems

Pienta's own research centers around what he calls "ecosystems" in metastatic cancer. "One of the reasons I came back to the Brady is to accelerate the pace of my own discoveries and come up with an effective ecological therapy that will modify the environment where the cancer cells are found." Most American men who are diagnosed with prostate cancer are cured by surgery or radiation, he notes, "but unfortunately, about 30,000 men still die of metastatic disease in this country every year. Many new drugs for metastatic prostate cancer have been approved in the last three years, but right now, we can't cure metastatic prostate cancer," and the reason may be that the drugs target the wrong aspects of cancer. "The majority of these therapies attack mutations in the cancer cells." But Pienta has come to believe that tumors can be viewed as ecosystems "where the cancer cells are intimately interacting with a variety of normal cells." In this microenvironment of a tumor within the body, he adds, it's the plain old regular cells that help the cancer grow and spread. The interaction of these cancerous and normal cells actually remodels the microenvironment. "Think of it as an evolving ecosystem," he explains. "We are using this model to design new treatments for metastatic prostate cancer," developing combination drugs that directly target the cancer cells and also attack the microenvironment. "For example, we discovered that almost half of cells in metastatic cancer sites are ‘tumor associated macrophages' – cells that should not even be there and have been attracted there to try and clean up the damage being done to the normal tissue by the cancer." Once these cells have been lured to the cancer site, they are co-opted – impressed, like the Shanghaied sailors of old – by the cancer cells to help the tumor grow. "We have already conducted two trials to block these macrophages as a way to treat prostate cancer and are working on multiple new therapies. We refer to this as ecological therapy for cancer."

Pienta is excited about the promise of these multi-targeting drugs. "There is great potential for us to make an exponential leap if we solve issues of drug combinations and figure out how to use targeted therapy correctly. I believe we will discover many innovative treatments, and transition them all the way from the bench to the bedside."





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